A new paradigm of quality of care in rheumatoid arthritis: how our new therapeutics have changed the game

Demonstrating the effectiveness of expensive new rheumatoid arthritis (RA) therapeutics is imperative to determine whether the quality of care has improved with the introduction of these agents. Our current RA quality measures are primarily process based, but they must become outcomes based to better demonstrate quality. New RA quality measures must be multidimensional, accounting for all of the important outcomes in RA: radiographic, functional status, and disease activity. To fully understand the potential benefits of new therapeutics in RA, outcome measures must be integrated with routine practice.New medications for rheumatoid arthritis (RA), combined with early, aggressive treatment strategies, have improved care. New biologic and small molecule therapies come with a hefty price tag, and demonstrating effectiveness is increasingly important: is the quality of care actually better for RA patients with newer therapies?To answer this question, we must first define quality. As described by the Institute of Medicine, quality of care is ''the degree to which healthcare services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge’ [1]. Quality of care can be evaluated using quality measures, which are tools that provide the ability to quantify an aspect of healthcare relative to an established criterion [2]. Other facets of quality include patient satisfaction and access to care. Quality of care in RA is currently largely based on the use of process-based quality measures. For example: the frequency of disease-modifying anti-rheumatic drug (DMARD) prescribing in RA; the use of disease activity and functional status measures in routine practice; and laboratory monitoring frequency according to established recommendations. These RA quality measures are primarily derived from the Arthritis Foundation Starter Set and the Physician Quality Reporting Database RA measure set, but the American College of Rheumatology is actively developing a new RA measure set [3]. Although the current RA quality measures provide a reasonable starting point, they do not fully capture the spectrum of care quality for patients with RA in the United States.Measures of quality of care are evolving to include concepts such as clinical outcomes. Some even argue that our primary goal should be to provide value: the health outcomes achieved per dollar spent [4]. This newer model incorporates the total cost of providing care to patients for a specific condition over a defined time period, relative to the health outcome achieved. For example, in RA the total cost of care would include nonbiologic and biologic DMARDs, office visits, physical therapy and inpatient hospitalizations. But the real question is how to best define outcomes in a chronic, complex condition such as RA? Outcomes can be multidimensional, accounting for all facets of care for a RA patient: radiographic progression, improvement in functional status score, or a decrease in disease activity score. Radiographic progression is often discussed as an important outcome in randomized controlled trials of RA therapeutics, but it is not a routine part of clinical practice. Measurement of functional status using a standardized, validated instrument is an important patient-reported outcome, capturing key information about how RA impacts activities of daily living. Patient-reported outcomes are not used regularly in many busy, office practices despite the correlation with disease outcomes and mortality [5,6].While professional groups such as the American College of Rheumatology have made recommendations on the measurement of disease activity through the use of tools such as the Disease Activity Score-28, the Clinical Disease Activity Index, or the Routine Assessment of Patient Disease Activity 3, documenting sustained low disease activity or remission requires multiple measurements [7]. Encouraging rheumatologists to treat to target and moving patients from high disease activity to remission is just one dimension of RA outcomes. Each potential clinical outcome has strengths and limitations and probably cannot serve as a standalone measure, but taken together they provide a more nuanced portrait of RA quality of care.Moving from thinking about quality measures as process based to outcomes based is a significant challenge. To achieve good outcomes in RA using the new therapeutics in RA, one needs to consider the timing of therapy, the duration of treatment, and the co-existence of other medical conditions. Some patients may delay initiation of DMARD therapy due to fear of toxicity or lack of understanding of the risk/benefit profile; other patients may not be fully adherent to the treatment plan due to financial issues, socioeconomic factors or language barriers; and still others may not have access to rheumatology care until after they have sustained radiographic or functional damage from their RA. Since quality is often measured at the level of the rheumatologist, how do we risk adjust for these complex patient-related factors when evaluating outcomes in RA? Some rheumatologists see tertiary-care referral patients with longer disease duration, more treatment failures, and multiple co-morbidities. Developing appropriate case-mix adjustment tools to allow for meaningful comparison across providers is a huge task. We have learned that even for a simple quality measure such as whether RA patients receive a DMARD, this case-mix adjustment matters. When evaluating the quality measure on receipt of DMARDs for patients with RA, case-mix adjustment identified age, race and socioeconomic status as negative predictors of DMARD receipt [8].Even though the road will be tough, we must determine how to best measure outcomes in RA to assess quality of care. The expenditures associated with biologic treatments raise important questions for how to demonstrate the effectiveness of medications for RA. However, there are emerging data on RA patients remaining in remission with fewer doses or even cessation of biologic drugs, raising the possibility that we can improve value for patients by simultaneously achieving good health outcomes and decreasing the overall cost of care [9]. An important first step to showing that new therapeutics are translating into better quality of care is incorporating the use of quantitative measurement of disease activity and functional status into routine clinical practice. By regularly measuring possible RA outcome measures, such as disease activity and functional status, we can identify patients who are achieving poor outcomes and create strategies to re-design care delivery for those patients. For example, the use of intensive nurse outreach between regularly scheduled rheumatologist visits to document medication adherence, side effects and education may improve outcomes faster and facilitate treating to target. Developing clinical risk-adjustment tools for RA can help offset differences in patient case mix among rheumatologists.However, measuring outcomes presents major challenges for the healthcare system in general. Collecting structured data to allow quality assessment is not routine in many practices and would place new burdens on the already stressed healthcare system, adding costs and frustration. Furthermore, accurately assessing quality of care requires adjusting for case-mix severity. This is especially true if outcomes become the focus of quality assessment. Collecting the dataset required for case-mix adjustment further taxes the healthcare provider. In addition, there are unanswered questions that remain: what is the current natural history of RA if diagnosed early and treated aggressively with combination nonbiologic and biologic DMARDs? To fully achieve the potential benefits of new therapeutics in RA, we first need RA quality measures that incorporate outcomes and these need to be easily integrated into typical practice.     

Expression and function of cell cycle proteins in rheumatoid arthritis synovial tissue

Rheumatoid Arthritis (RA) is a chronic disease characterised by synovial lining hyperplasia and progressive destruction of joint tissues. Experimental data suggests that abnormal alterations in the expression of proteins involved in maintaining homeostatic control of the cell cycle is involved in disease progression in RA. By contributing to the overgrowth of synovial tissue, factors such as dysregulated proliferation or reduced apoptosis of cells can directly influence the pathological outcome of RA.     

Which patients with rheumatoid arthritis are still working?

In the light of improved and costly treatment for rheumatoid arthritis (RA), the evaluation of work disability has gained increased attention. The assumption that better treatment of RA leads to increased work participation has not yet been supported by sufficient evidence. Differences in RA-related work disability have been observed between countries, also indicating an influence of non-disease-related macroeconomic factors. Work disability results from a complex interaction between a clinical disease, sociodemographic variables, macroeconomic conditions, and personal factors. Some of these factors are modifiable, while others are not.     

Predicting shiftwork-related outcomes: shiftwork locus of control and circadian type

This research discusses the use and viability of the shiftwork locus of control construct alongside circadian type measures as a potential predictor of shiftwork-related outcomes. The shiftwork locus of control (SHLOC) scale, measures of circadian type and shiftwork-related outcome measures were completed by 100 shiftworkers on two occasions separated by seven months. The SHLOC scale measures shiftworkers' generalised beliefs about the levels of personal control they perceive in relation to four major functional domains commonly associated with shiftwork-related disruption. These domains include: sleep, social, health and work problems. The results of multivariate regression analysis showed the SHLOC scale to be predictive of the experience of shiftwork-related sleep and social-life problems while the circadian type measures were predictive of alertness at 7 months. The results suggest that a constellation of personality factors may be an important influence on an individual's tolerance to shiftwork.     

Truncated and constrained helical analogs of antimicrobial esculentin-2EM

Esculentin-2EM is a 37-residue, cationic, amphipathic, α-helical antimicrobial peptide isolated from a Korean frog, Glandirama emeljanovi. Many studies revealed that truncation of this peptide results in substantial decreases in its antimicrobial activity. Lee and his colleagues have recently reported that a 23-residue esculentin-2EM analog containing a tryptophanyl substitution at position 16 showed a significant recovery of the antimicrobial activity of the parent peptide. Here we report a new series of 15-residue esculentin-2EM analogs which are constrained into an α-helical conformation via an oct-4-enyl cross-link. The resulting ‘stapled’ derivatives displayed remarkable increases not only in antimicrobial activity but also in helical content and protease resistance compared to Lee’s original 23-residue esculentin-2EM analog. The preliminary data obtained in this work strongly supports the potential of our strategy for the development of a new class of peptide antibiotics.     

Are synovial biopsies of diagnostic value?

Synovial tissue is readily accessible by closed needle or arthroscopic biopsy. These techniques provide adequate tissue for most diagnostic requirements. Examination of synovial tissue can assist in the diagnosis of some joint infections, and in several atypical or rare synovial disorders. Histological confirmation is not normally required for diagnosis of the common forms of inflammatory arthritis, including rheumatoid arthritis (RA). In patients with either established or early RA, immunohistological measures of inflammation in synovial tissue are associated with clinical measures of disease activity, may predict the clinical outcome, and change in response to treatment. Surrogate markers of disease activity and outcome that have been identified in synovial tissue include components of the cellular infiltrate, and several mediators of inflammation and matrix degradation. There is evidence that the very early introduction of disease-modifying therapy inhibits progressive structural damage maximally. Clinicians exploiting this 'window of opportunity' therefore require very early indicators of the diagnosis and outcome in patients who present with an undifferentiated inflammatory arthritis. Some immunohistological features have been described that distinguish patients who are likely to develop progressive RA and who might benefit most from early aggressive therapeutic intervention. In this regard, the inclusion of pharmacogenomic and proteomic techniques in the analysis of synovial tissue presents some exciting possibilities for future research.     

The new era of autoimmune disease research

Recent genome-wide association studies have advanced our understanding of genetic factors that underlie systemic lupus erythematosus (SLE), a multifactorial autoimmune disease characterized by various clinical manifestations. SLE also has an environmental component, which can trigger or exacerbate the disease. Despite extensive efforts aimed at elucidating the cellular and biological abnormalities that arise in the immune system of patients with SLE, its pathology remains unclear. Lee and colleagues recently carried out gene expression profiling of patients with SLE followed by bioinformatics analysis and discovered the existence of abnormal regulatory networks and potential key molecules. The authors found that ATP synthesis and DNA repair pathways may be involved in the pathogenesis, providing a potential explanation for photosensitivity experienced by patients with SLE.     

Cardiovascular risk management in rheumatoid arthritis: are we still waiting for the first step?

Rheumatoid arthritis (RA) is associated with a similar cardiovascular risk to that in diabetes, and therefore cardiovascular risk management (CV-RM) - that is, identification and treatment of cardiovascular risk factors (CRFs) - is mandatory. However, whether and to what extent this is done in daily clinical practice is unknown. In a retrospective cohort investigation, CV-RM was therefore compared between rheumatologists and primary care physicians (PCPs). Remarkably, CRFs in RA were less frequently identified and managed by rheumatologists in comparison with PCPs. In addition, PCPs assessed CRFs less frequently in RA than in diabetes. Obviously, there is a clear need for improvement of CV-RM in RA and this should be a joint effort from the rheumatologist and the PCP.Patients with rheumatoid arthritis (RA) have an increased cardiovascular (CV) risk that appears similar to that in diabetes. This observation highlights the significant CV burden in RA. In 1999, the American Diabetes Association and the American Heart Association published a statement for prevention of CV disease in diabetes. Since then, the CV risk in diabetes has been substantially lower than in earlier decades. Given the increased CV risk in RA, screening, identification of cardiovascular risk factors (CRFs) and cardiovascular risk management (CV-RM) are also highly needed as recommended by the European League Against Rheumatism (EULAR). The increased risk in RA is attributed to systemic inflammation as well as increased prevalence of CRFs. Hence, we should aim for tight disease control and control of CRFs.Presently unknown is whether and to what extent CV-RM is translated into clinical practice. In a retrospective cohort-comprising 251 patients with RA, 251 patients with diabetes, and 251 general population individuals-Desai and colleagues therefore investigated the identification and management of CRFs by rheumatologists and primary care physicians (PCPs) [1]. RA patients had to be registered at the University of Michigan Health System for at least 12 months between June 2007 and April 2012 and had been evaluated both by their rheumatologist as well as the PCP. CRFs of interest were smoking, exercise, weight, blood pressure, lipid profile, and fasting blood glucose.In RA, PCPs identified and managed most CRFs more frequently than rheumatologists. Secondly, identification of CRFs by rheumatologists in RA patients with elevated C-reactive protein levels was not different as compared with those with normal C-reactive protein levels. A third important observation was that PCPs identified and managed CRFs more frequently in patients with diabetes, followed by general population individuals and least often in RA patients. These striking results raise several issues.First, it is hard to believe that the largely absent CV-RM by rheumatologists is explained by under-recognition because the increased CV risk in RA must presently be well known among rheumatologists. A large amount of literature on this topic has been published over the last decade. Additionally, the necessity to screen, identify, and manage CRFs is incorporated into training programmes for rheumatology residents [2]. Against this background, it is important to realise that there is a lag time between the publication of the EULAR guideline and its actual implementation (that is, the guideline was published in 2010 [3] while the current study started in 2007). In other words, CV-RM in today''s clinical practice might have been improved, but not yet recognised.Second, that the CV risk in RA is related to the inflammatory burden is well known. Nevertheless, the present study did not indicate that there is more attention for CV-RM by rheumatologists in patients with a higher inflammatory load.Third, undertreatment of the increased CV risk in RA by PCPs might be explained by under-recognition because CRFs were assessed more frequently in diabetes in comparison with RA.The EULAR guidelines recommend screening and identification of CRFs in all RA patients, and, if indicated according to CV risk-prediction charts, adequate management. As accurate assessment of CV risk depends on RA characteristics, the EULAR favoured individualising risk assessment. Hence, a risk multiplication factor of 1.5 should be used in the presence of two of the following criteria: disease duration >10 years, rheumatoid factor, and/or anti-cyclic citrullinated peptide positivity or the presence of extra-articular manifestations. However, alternative approaches have been suggested - for example, increasing the age of an RA patient by 10 years to obtain a more precise CV risk estimate or to use other risk scores. Perhaps this lack of an RA-specific CV risk-prediction model hampers CV-RM implementation. Obviously, this discussion can only be solved by developing a RA-specific CV risk-prediction model, but this will take several years to complete.One may obviously argue that, due to its retrospective design, the strength of the conclusions of Desai and colleagues may be limited; however, they are in line with other recently published literature and thus confirm extending evidence that CV-RM is poorly conducted in RA, both by rheumatologists and PCPs. Another argument against CV-RM in RA is that we should wait until trials have been conducted that demonstrate the efficacy of statins and antihypertensive agents in RA. However, it will be (many) years before specific risk models are available and withholding cardiopreventive drugs that are very likely to work also in our high-risk population is unethical. Moreover, it is important to realise that, due to the decreased incidence of CV events in the last decades, CV prevention trials are nowadays very difficult to conduct. For instance, the TRACE-RA study [4] - a large placebo-controlled double-blind primary CV prevention trial in RA with atorvastatin - was stopped prematurely owing to the very low number of CV events that occurred.Altogether, the study from Desai and colleagues provides three important clues for improvement of CV-RM in RA. First, more education is urgently needed for both rheumatologists and PCPs. Second, it is important to realise that the contribution of higher prevalence CRFs in RA is one side of the coin, but the other side is effective suppression of the inflammation. The latter is a clear task for the rheumatologist. Third, CV care of a RA patient should be a joint effort by the rheumatologist and the PCP, and they should collaborate and agree on who performs the screening, identification, and, if required, management of CRFs.     

Circulating cytokine pattern and factors describing rheumatoid arthritis: IL-15 as one of the biomarkers for RA?

The aim of study was to examine relationship among levels of cytokines (IL-6, IL-13, IL-15, TNF-α) and chemokine (IL-8), production of autoantibodies, radiographic progression, and factors describing rheumatoid arthritis (RA). A total of 156 RA patients according to ACR criteria, and 55 control subjects were recruited into study. We observed higher levels of IL-15 within RA patients compared to healthy controls. Correlations among cytokine levels and the measures of rheumatoid factors, anti-CCP, measures of disease activity, and radiographic progression were observed. We conclude that IL-15 level in circulation could serve as one of the biomarkers for RA detection.     

Moving towards personalized medicine in rheumatoid arthritis

To develop personalized medicine strategies for improvement of patient management in rheumatoid arthritis, the clinical and molecular properties of the individual patients need to be well characterized. A crucial step in this approach is to discover subgroups of patients that are characterized by a good or poor treatment outcome. Dennis and colleagues have identified distinct pretreatment gene expression profiles in affected synovial tissue specimens and a tissue type-related systemic protein pattern which are associated with a positive or negative clinical outcome to monotherapy with adalumimab (anti-TNFα) and tocilizumab (anti-IL-6 receptor). These observations assign biological pathways associated with response outcome and provide evidence for the existence of systemic, easy-to-measure predictive biomarkers for clinical benefit of these biologics.     

Fishery discards: factors affecting their variability within a demersal trawl fishery

Discards represent one of the most important issues within current commercial fishing. It occurs for a range of reasons and is influenced by an even more complex array of factors. We address this issue by examining the data collected within the Danish discard observer program and describe the factors that influence discarding within the Danish Kattegat demersal fleet over the period 1997 to 2008. Generalised additive models were used to assess how discards of the 3 main target species, Norway lobster, cod and plaice, and their subcomponents (under and over minimum landings size) are influenced by important factors and their potential relevance to management. Our results show that discards are influenced by a range of different factors that are different for each species and portion of discards. We argue that knowledge about the factors influential to discarding and their use in relation to potential mitigation measures are essential for future fisheries management strategies.     

Methotrexate therapy associates with reduced prevalence of the metabolic syndrome in rheumatoid arthritis patients over the age of 60- more than just an anti-inflammatory effect? A cross sectional study

Introduction  

The metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in rheumatoid arthritis (RA). The prevalence and associations of the MetS in RA remain uncertain: systemic inflammation and anti-rheumatic therapy may contribute. Methotrexate (MTX) use has recently been linked to a reduced presence of MetS, via an assumed generic anti-inflammatory mechanism. We aimed to: assess the prevalence of the MetS in RA; identify factors that associate with its presence; and assess their interaction with the potential influence of MTX.     

Religious Coping with Chronic Pain

This study examined the role of religious and nonreligious cognitive-behavioral coping in a sample of 61 chronic pain patients from a midwestern pain clinic. Participants described their chronic pain and indicated their use of religious and nonreligious cognitive-behavioral coping strategies. Results supported a multidimensional conceptualization of religious coping that includes both positive and negative strategies. Positive religious coping strategies were associated significantly with positive affect and religious outcome after statistically controlling for demographic variables. In contrast, measures of negative religious coping strategies were not associated significantly with outcome variables. Several significant associations also were found between nonreligious cognitive-behavioral coping strategies and outcome variables. The results underscore the need for further research concerning the contributions of religious coping in adjustment to chronic pain. Practitioners of applied psychophysiology should assess their chronic pain patients' religious appraisals and religious coping as another important stress management strategy.     

The relationship between cancer and rheumatoid arthritis: still a large research agenda

The association between rheumatoid arthritis (RA) and malignancies has received increased attention in recent years. Reports suggesting that tumor necrosis factor blockers might elevate the risk of malignancy in RA patients have prompted researchers to look at the incidence of malignancies in all RA patients. In a recent issue of Arthritis Research & Therapy, Smitten and colleagues suggest that previous reports of a standardized incidence ratio close to one for malignancies in RA may reflect an increased risk for some site-specific malignancies and a reduced risk for others. Here we discuss these findings and suggest what issues could be addressed in future studies.     

Baseline serum MMP-3 levels in patients with Rheumatoid Arthritis are still independently predictive of radiographic progression in a longitudinal observational cohort at 8 years follow up

Introduction  

At present, there is no reliable tool for predicting disease outcome in patients with rheumatoid arthritis (RA). We previously demonstrated an association between specific baseline biomarkers/clinical measures including matrix metalloproteinase-3 (MMP-3) and 2-year radiographic progression in patients with RA. This study further evaluates the predictive capability of these baseline variables with outcome extended over 8-years.     

Evolution and nature of science instruction

In this article, I provide an analysis of my work (1985–present) with non-major biology students and science teacher candidates in developing strategies for teaching and enhancing learning with respect to evolutionary science. This first-person account describes changes in evolution instruction over the course of a career based on personal experiences, research-informed practices, and a critical collaboration with colleague Mike U. Smith. I assert four insights concerning the influence and efficacy of teaching nature of science (NOS) prior to the introduction of evolution within college courses for science non-majors and science teacher candidates. These insights are: (a) teach explicit NOS principles first; (b) integrate evolution as a theme throughout a course in introductory biology (but after NOS principles have been introduced); (c) use active learning pedagogies; and (d) use non-threatening alternative assessments to enhance student learning and acceptance of evolutionary science. Together, these insights establish a pedagogy that I (and my colleagues) have found to be efficacious for supporting novice students as they engage in the study of evolutionary science.